The Wellcome Trust Discovery Award scheme provides funding for established researchers to pursue bold and creative research ideas and deliver significant shifts in understanding that could improve human life, health and wellbeing.
Professor of Neuroscience Randy Bruno will use his Award to investigate the mediator of cognition, the neocortex, the largest part of the cerebral cortex responsible for a diverse set of abilities including sensation, perception, decision making, planning, and movement. Dysfunctions of neocortex are thought to underlie numerous neurological and psychiatric disorders. All neocortical areas share a common laminar architecture, with stereotyped patterns of connectivity linking any given layer with another layer, or with other nervous system structures. The computational and behavioural roles of the different layers have largely remained enigmatic.
Professor Bruno said: "My Discovery Award has two goals. The first is to understand how the cortical layers flexibly support multiple complex behaviours while allowing us to generalise to situations we’ve never seen before. The second goal is to understand the cellular and circuit mechanisms by which learning rewires the cortical layers in task-specific ways. Our study will contribute to new frameworks for understanding how all neocortical areas enable behaviour and how various disorders disrupt cognitive processing.
“Wellcome recognises the value of a scientific funding model that provides a high level of support and flexibility for an entire lab, rather than funding one small specific project. Only with that degree of investment can a laboratory pivot quickly to attempt something new that might be incredibly important to its overall goals. The support of a Discovery Award, along with its long time horizon, can unleash unexpected creativity and discovery. I’m deeply honoured that Wellcome and its scientific advisors believe so strongly in our greater mission to give my lab and me the chance to make those kinds of contributions.”
Professor of Neurobiology Scott Waddell will use his Award to get to the heart of the neural mechanisms behind memory and motivation. The Waddell Lab's studies using the common fruit fly (Drosophila) have discovered that heterogeneity of the dopaminergic system is a fundamental organising principle of mnemonic networks, in particular they have identified how parallel combinations of dopaminergic neurons reinforce memories defined by valence and specific types of reward, and control how these memories are expressed. Opponent neurons update these memories when learned expectations are not met. The Waddell Lab recently contributed to the generation of a synapse-level connectome, or wiring diagram of the fly brain's neural connections, revealing an unprecedented level of complexity of memory networks that provides a functional logic for their studies.
Waddell's team of researchers are applying single-cell sequencing approaches to discover a key piece of information that is missing from the physical connectome, known as the 'wireless' neuromodulatory network. In their proposed work, they will determine how internal motivational states engage the neuromodulatory network to orchestrate and select activity within wired subcircuits of the dopaminergic system, to instruct appropriate formation and expression of different kinds of memory. They will also establish how breakdown of control in the dopaminergic system produces inappropriate behaviours, such as compulsive reward-seeking.
Professor Waddell said: "These experiments and approaches will transform our understanding of the molecular, cellular and network-level operating principles that permit diversity in the dopaminergic system to coordinate parallel state-dependent memory networks. Dysfunction within a heterogeneous system is likely to underlie the diversity of roles implicated for dopamine in numerous neurological and psychiatric disorders in humans.
"I'm honoured and absolutely delighted to receive a Wellcome Discovery Award, following my Senior and Principal Research Fellowships in Basic Biomedical Sciences. This recognition belongs to the long list of past and present techs, students and postdocs in my group and I'm relieved that I can continue to support them! I think this is a truly golden-age for our research of the neural mechanisms of memory and we're all really excited about what lies ahead."
The Wellcome Trust Discovery Awards will facilitate the Bruno and Waddell teams for the next eight years.